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https://www.readbyqxmd.com/read/29454156/the-glun2b-subunit-represents-a-major-functional-determinant-of-nmda-receptors-in-human-induced-pluripotent-stem-cell-derived-cortical-neurons
#1
Ioana Neagoe, Chang Liu, Alexander Stumpf, Yanmei Lu, Dongping He, Ross Francis, Jun Chen, Paul Reynen, Moulay Hicham Alaoui-Ismaili, Hirokazu Fukui
Abnormal signaling pathways mediated by N-methyl-d-aspartate receptors (NMDARs) have been implicated in the pathogenesis of various CNS disorders and have been long considered as promising points of therapeutic intervention. However, few efforts have been previously described concerning evaluation of therapeutic modulators of NMDARs and their downstream pathways in human neurons with endogenous expression of NMDARs. In the present study, we assessed expression, functionality, and subunit composition of endogenous NMDARs in human induced pluripotent stem cell (hiPSC)-derived cortical neurons (iCell Neurons and iCell GlutaNeurons)...
February 8, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29454093/silencing-circular-rna-hsa_circ_0000977-suppresses-pancreatic-ductal-adenocarcinoma-progression-by-stimulating-mir-874-3p-and-inhibiting-plk1-expression
#2
Wen-Jie Huang, Yun-Chao Wang, Song-Song Liu, Jia-Li Yang, Shi-Xiang Guo, Li-Jiang Wang, Huai-Zhi Wang, Ying-Fang Fan
Circular RNAs (CircRNAs) are a novel type of endogenous noncoding RNAs that regulate target gene expression by interacting with microRNA (miRNA). Emerging evidence shows that dysregulation of circRNAs plays important roles in biological and pathological processes, including cancer development and progression. The functional role of circRNA in PDAC (pancreatic ductal adenocarcinoma) remains to be investigated. In this study, high throughput microarray assay revealed that hsa_circ_0000977 was aberrantly up-regulated in pancreatic cancer tissues; this was also validated by qRT-PCR...
February 14, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29454088/hsf4-transcriptional-regulates-hmox-1-expression-in-hlecs
#3
Shengjie Liao, Zhen Qu, Linqiang Li, Benwen Zhou, Meng Gao, Mi Huang, Duanzhuo Li
The major causes for cataract formation are free radicals, which are neutralized by the endogenous antioxidants. However, how the human lens clean these harmful free radicals is still unclear. Transcriptional factor heat shock factor 4 (HSF4) is a cataract-causing gene and plays important roles during lens development. Here we show that HMOX-1, an anti-oxidase, is a bona fide transcriptional target gene of HSF4 in HLECs (human lens epithelial cells). HSF4 directly binds to the HSE element in HMOX-1 promoter to mediate its mRNA transcription and protein accumulation...
February 14, 2018: Gene
https://www.readbyqxmd.com/read/29454075/the-g-protein-coupled-p2y-6-receptor-promotes-colorectal-cancer-tumorigenesis-by-inhibiting-apoptosis
#4
Morgane Placet, Guillaume Arguin, Caroline M Molle, Jean-Philippe Babeu, Christine Jones, Julie C Carrier, Bernand Robaye, Sameh Geha, Francois Boudreau, Fernand-Pierre Gendron
Colorectal tumors are immersed in an array of tumor-promoting factors including extracellular nucleotides such as uridine 5'‑diphosphate (UDP). UDP is the endogenous agonist of the G protein-coupled P2Y 6 receptor (P2Y 6 R), which may contribute to the formation of a tumor-promoting microenvironment by coordinating resistance to apoptosis. Colorectal cancer (CRC) was chemically induced in P2ry6 knockout (P2ry6 -/- ) mice using azoxymethane and dextran sulfate sodium challenges. Mice were euthanatized and their tumor load determined...
February 14, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29453900/downregulation-of-reticulocalbin-1-differentially-facilitates-apoptosis-and-necroptosis-in-human-prostate-cancer-cells
#5
Xiaofei Liu, Nianzhao Zhang, Dawei Wang, Deyu Zhu, Quan Yuan, Xiulei Zhang, Lilin Qian, Huanmin Niu, Yi Lu, Guijie Ren, Keli Tian, Huiqing Yuan
Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca 2+ -binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with Cyclin B, not Cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively...
February 17, 2018: Cancer Science
https://www.readbyqxmd.com/read/29453815/the-use-of-chitosan-porous-3d-scaffolds-embedded-with-resolvin-d1-to-improve-in-vivo-bone-healing
#6
Daniela P Vasconcelos, Madalena Costa, Nuno Neves, José H Teixeira, Daniel M Vasconcelos, Susana G Santos, Artur P Águas, Mário A Barbosa, Judite N Barbosa
The aim of this study was to investigate the effect chitosan (Ch) porous 3D scaffolds embedded with resolvin D1 (RvD1), an endogenous pro-resolving lipid mediator, on bone tissue healing. These scaffolds previous developed by us have demonstrated to have immunomodulatory properties namely in the modulation of the macrophage inflammatory phenotypic profile in an in vivo model of inflammation. Herein, results obtained in an in vivo rat femoral defect model demonstrated that two months after Ch+RvD1 scaffolds implantation, an increase in new bone formation, in bone trabecular thickness, and in collagen type I and Coll I/Coll III ratio were observed...
February 17, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29453798/melatonin-protects-against-defects-induced-by-deoxynivalenol-during-mouse-oocyte-maturation
#7
Mei Lan, Jun Han, Meng-Hao Pan, Xiang Wan, Zhen-Nan Pan, Shao-Chen Sun
Deoxynivalenol (DON) is one of the most prevalent Fusarium mycotoxins in feedstuff and food. DON causes detrimental effects on human and animal reproductive systems by inducing oxidative stress and apoptosis. While melatonin is a multifunctional endogenous hormone which plays crucial roles in the development of animal germ cells and embryos as a robust deoxidizer. In present study, we explored the effects of melatonin on the DON-exposure mouse oocytes. Our in vitro and in vivo results showed that DON adversely affected mouse oocyte maturation and early embryo cleavage, while melatonin administration ameliorated the toxic effects of DON...
February 17, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29453779/mitochondrial-cytochrome-p450-cyp-1b1-is-responsible-for-melatonin-induced-apoptosis-in-neural-cancer-cells
#8
Zhenlong Yu, Xiangge Tian, Yuling Peng, Zheng Sun, Chao Wang, Ning Tang, Bin Li, Yuqing Jian, Wei Wang, Xiaokui Huo, Xiaochi Ma
Melatonin is an endogenous indoleamine with a wide range of biological functions in the various organisms from bacteria to mammals. Evidence indicates that melatonin facilitates apoptosis in cancer cells and enhances the anti-tumor activity of chemotherapy in animals and clinical studies. However, the melatonin metabolism and the key metabolic targets in cancer cells still remain unknown. In this study, U118 and SH-SY5Y tumor cell lines were used to investigate the metabolic pathways of melatonin in cancer cells...
February 17, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29453733/egfp-transgene-a-useful-tool-to-track-transplanted-bone-marrow-mononuclear-cell-contribution-to-peripheral-remyelination
#9
Gonzalo Piñero, Vanina Usach, Paula A Soto, Paula V Monje, Patricia Setton-Avruj
Bone marrow mononuclear cells (BMMC) constitute a heterogeneous population with potential to promote tissue regeneration. For this reason, this cell fraction has recently become a therapeutic alternative to mesenchymal stem cells, as culture is not required and phenotypic transformations can be hence avoided. In this work, and in order to attain long-lasting cell labeling and study longer survival times, we used BMMC isolated from adult transgenic rats expressing GFP to reproduce our wild type model and evaluate their remyelination ability in a reversible model of Wallerian degeneration...
February 16, 2018: Transgenic Research
https://www.readbyqxmd.com/read/29453611/comparative-study-of-phototoxicity-of-protoporphyrin-ix-synthetic-and-extracted-from-ssp-rattus-novergicus-albinus-rats-toward-murine-melanoma-cells
#10
E R Reis, L P Ferreira, E M D Nicola, I Borissevitch
Protoporphyrin IX (PpIX) is a precursor of heme synthesis and is known to be an active photosensitizer and precursor of photosensitizers applied in photodynamic therapy (PDT) and photodynamic diagnostics (PDD). On irradiation with visible light, PpIX undergoes phototransformation, producing photoproducts which may also be phototoxic and increase its efficacy. The mechanism of PpIX phototransformation depends on environmental characteristics and can be different in vitro and in vivo. In this paper, we present a comparative study of the photoactivity of synthetic PpIX and PpIX extracted from the Harderian gland of ssp Rattus novergicus albinus rats, along with their photoproducts toward murine B16F-10 melanoma cells...
February 16, 2018: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/29453456/loss-of-microrna-128-promotes-cardiomyocyte-proliferation-and-heart-regeneration
#11
Wei Huang, Yuliang Feng, Jialiang Liang, Hao Yu, Cheng Wang, Boyu Wang, Mingyang Wang, Lin Jiang, Wei Meng, Wenfeng Cai, Mario Medvedovic, Jenny Chen, Christian Paul, W Sean Davidson, Sakthivel Sadayappan, Peter J Stambrook, Xi-Yong Yu, Yigang Wang
The goal of replenishing the cardiomyocyte (CM) population using regenerative therapies following myocardial infarction (MI) is hampered by the limited regeneration capacity of adult CMs, partially due to their withdrawal from the cell cycle. Here, we show that microRNA-128 (miR-128) is upregulated in CMs during the postnatal switch from proliferation to terminal differentiation. In neonatal mice, cardiac-specific overexpression of miR-128 impairs CM proliferation and cardiac function, while miR-128 deletion extends proliferation of postnatal CMs by enhancing expression of the chromatin modifier SUZ12, which suppresses p27 (cyclin-dependent kinase inhibitor) expression and activates the positive cell cycle regulators Cyclin E and CDK2...
February 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29453373/dormancy-release-and-germination-of-taxus-yunnanensis-seeds-during-wet-sand-storage
#12
Fangyuan Bian, Jianrong Su, Wande Liu, Shuaifeng Li
Dormancy is an innate constraint on germination that occurs across all life forms. In this study, we investigated the seed dormancy release and germination characters of Taxus yunnanensis by exploring the seed morphology, permeability, germination inhibitors, endogenous hormones, and embryo germination in vitro during wet sand storage. Our results showed that seeds and embryos grew to a critical size to germination and permeability increased with the extension of storage. Seed coat and kernel methanol extracts reduced Brassica campestris seed vigor index...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453333/scleraxis-is-a-transcriptional-activator-that-regulates-the-expression-of-tenomodulin-a-marker-of-mature-tenocytes-and-ligamentocytes
#13
Chisa Shukunami, Aki Takimoto, Yuriko Nishizaki, Yuki Yoshimoto, Seima Tanaka, Shigenori Miura, Hitomi Watanabe, Tetsushi Sakuma, Takashi Yamamoto, Gen Kondoh, Yuji Hiraki
Tenomodulin (Tnmd) is a type II transmembrane glycoprotein predominantly expressed in tendons and ligaments. We found that scleraxis (Scx), a member of the Twist-family of basic helix-loop-helix transcription factors, is a transcriptional activator of Tnmd expression in tenocytes. During embryonic development, Scx expression preceded that of Tnmd. Tnmd expression was nearly absent in tendons and ligaments of Scx-deficient mice generated by transcription activator-like effector nucleases-mediated gene disruption...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453283/chemical-stresses-fail-to-mimic-the-unfolded-protein-response-resulting-from-luminal-load-with-unfolded-polypeptides
#14
Timothy J Bergmann, Ilaria Fregno, Fiorenza Fumagalli, Andrea Rinaldi, Francesco Bertoni, Paul J Boersema, Paola Picotti, Maurizio Molinari
The stress sensors ATF6, IRE1 and PERK monitor deviations from homeostatic conditions in the endoplasmic reticulum (ER), a protein biogenesis compartment of eukaryotic cells. Their activation elicits unfolded protein responses (UPR) to re-establish proteostasis. UPR have been extensively investigated in cells exposed to chemicals that activate ER stress sensors by perturbing calcium, N-glycans or redox homeostasis. Cell responses to variations in luminal load with unfolded proteins are, in contrast, poorly characterized...
February 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29453275/structure-based-discovery-of-selective-positive-allosteric-modulators-of-antagonists-for-the-m-2-muscarinic-acetylcholine-receptor
#15
Magdalena Korczynska, Mary J Clark, Celine Valant, Jun Xu, Ee Von Moo, Sabine Albold, Dahlia R Weiss, Hayarpi Torosyan, Weijiao Huang, Andrew C Kruse, Brent R Lyda, Lauren T May, Jo-Anne Baltos, Patrick M Sexton, Brian K Kobilka, Arthur Christopoulos, Brian K Shoichet, Roger K Sunahara
Subtype-selective antagonists for muscarinic acetylcholine receptors (mAChRs) have long been elusive, owing to the highly conserved orthosteric binding site. However, allosteric sites of these receptors are less conserved, motivating the search for allosteric ligands that modulate agonists or antagonists to confer subtype selectivity. Accordingly, a 4.6 million-molecule library was docked against the structure of the prototypical M 2 mAChR, seeking molecules that specifically stabilized antagonist binding. This led us to identify a positive allosteric modulator (PAM) that potentiated the antagonist N -methyl scopolamine (NMS)...
February 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29453096/design-of-mitochondria-targeted-colorimetric-and-ratiometric-fluorescent-probes-for-rapid-detection-of-so-2-derivatives-in-living-cells
#16
Yutao Yang, Tingting Zhou, Bozan Bai, Caixia Yin, Wenzhi Xu, Wei Li
Two mitochondria-targeted colorimetric and ratiometric fluorescent probes for SO 2 derivatives were constructed based on the SO 2 derivatives-triggered Michael addition reaction. The probes exhibit high specificity toward HSO 3 - /SO 3 2- by interrupting their conjugation system resulting in a large ratiometric blue shift of 46-121nm in their emission spectrum. The two well-resolved emission bands can ensure accurate detection of HSO 3 - . The detection limits were calculated to be 1.09 and 1.35μM. Importantly, probe 1 and probe 2 were successfully used to fluorescence ratiometric imaging of endogenous HSO 3 - in BT-474 cells...
February 13, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29453091/identification-of-mirnas-and-their-targets-in-maize-in-response-to-sugarcane-mosaic-virus-infection
#17
Zihao Xia, Zhenxing Zhao, Mingjun Li, Ling Chen, Zhiyuan Jiao, Yuanhua Wu, Tao Zhou, Weichang Yu, Zaifeng Fan
MicroRNAs (miRNAs) are endogenous non-coding small RNAs that play essential regulatory roles in plant development and environmental stress responses. Maize (Zea mays L.) is a global economically important food and forage crop. To date, a number of maize miRNAs have been identified as being involved in plant development and stress responses. However, the miRNA-mediated gene regulatory networks responsive to virus infections in maize remain largely unknown. In this study, the profiles of small RNAs in buffer- and Sugarcane mosaic virus (SCMV)-inoculated maize plants were obtained by high-throughput sequencing, respectively...
January 31, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29452699/hypolipidemic-components-from-medicine-food-homology-species-used-in-china-pharmacological-and-health-effects
#18
REVIEW
De-Xing Song, Jian-Guo Jiang
Hyperlipidemia is a systemic disease caused by abnormal human lipid metabolism. Dietary control and treatment on hyperlipidemia is now a popular therapy pathway. This paper focuses on the medicine food homology (MFH) species used in China with hypolipidemic function, and emphasizes on the active ingredients and their pharmacological effect. The single herbal and its hypolipidemic active ingredients are summarized through reviewing the relevant literatures published in the past twenty years. The ingredients are divided into polysaccharides, flavonoids, steroidal saponins, quinones, alkaloids and others, of which the related researches are described from the aspects of sources, model and method, result and mechanisms, respectively...
February 13, 2018: Archives of Medical Research
https://www.readbyqxmd.com/read/29452639/mitochondrial-mdm2-regulates-respiratory-complex-i-activity-independently-of-p53
#19
Giuseppe Arena, Madi Yann Cissé, Samuel Pyrdziak, Laurent Chatre, Romain Riscal, Maryse Fuentes, Jamie Jon Arnold, Markus Kastner, Laurie Gayte, Christelle Bertrand-Gaday, Kevin Nay, Claire Angebault-Prouteau, Kerren Murray, Beatrice Chabi, Christelle Koechlin-Ramonatxo, Béatrice Orsetti, Charles Vincent, François Casas, Jean-Christophe Marine, Sandrine Etienne-Manneville, Florence Bernex, Anne Lombès, Craig Eugene Cameron, Hervé Dubouchaud, Miria Ricchetti, Laetitia Karine Linares, Laurent Le Cam
Accumulating evidence indicates that the MDM2 oncoprotein promotes tumorigenesis beyond its canonical negative effects on the p53 tumor suppressor, but these p53-independent functions remain poorly understood. Here, we show that a fraction of endogenous MDM2 is actively imported in mitochondria to control respiration and mitochondrial dynamics independently of p53. Mitochondrial MDM2 represses the transcription of NADH-dehydrogenase 6 (MT-ND6) in vitro and in vivo, impinging on respiratory complex I activity and enhancing mitochondrial ROS production...
February 15, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29452635/the-circulating-protease-persephone-is-an-immune-sensor-for-microbial-proteolytic-activities-upstream-of-the-drosophila-toll-pathway
#20
Najwa Issa, Nina Guillaumot, Emilie Lauret, Nicolas Matt, Christine Schaeffer-Reiss, Alain Van Dorsselaer, Jean-Marc Reichhart, Florian Veillard
Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila, genetic evidences indicate that the serine protease Persephone belongs to a danger pathway activated by abnormal proteolytic activities to induce Toll signaling. However, neither the activation mechanism of this pathway nor its specificity has been determined...
February 15, 2018: Molecular Cell
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